99 Specific (Adaptive) Immunity – Sensitization of B Cells and Activation of B cells by Helper T Cells

Sensitization of B cells:

B cells become sensitized after they phagocytose either pathogen (bacteria, virus) or pathogen antigens.   This is done with the help of IgD antibody receptors (B cell receptors, BCRs) that bind to specific non-self antigens.  Most often these non-self antigens belong to pathogens such as bacteria.  Once the bacteria is phagocytosed, the bacteria is degraded and bacterial peptides are bound to MHC II molecules and sent to the B cell surfaces for display.  The B cell is now termed “sensitized”. 

BCRs actually have a dual role, in that not only do they assist in internalizing pathogens, once they attach to a pathogen, they also stimulate DNA expression of genes required for B cell activity.

CD4+ Helper T cell Activation of Sensitized B cells that are Displaying Non-Self Antigens:

Once sensitized, B cells can be activated by activated Helper CD4+ T cells, which do this by using their TCR and CD4 co-receptors to bind to the peptide-MHC II molecules on the surface of the B cell.  This recognition of a non-self peptide display by the B cell’s MHC II, triggers the Helper CD4+ T cell to release cytokines (e.g. lymphokines, specifically interleukins) that activate the B cell.  The activated B cell will proliferate producing 2 types of daughter cells:

• • Plasmablasts which differentiate (mature) into Plasma cells that become antibody factories, producing antibodies against the specific bacterial antigens.  Plasma cells can produce ¬100 million antibodies per hour.  The release of different cytokines by Helper T cells is thought to help stimulate which type of antibodies are produced (IgG, IgA, IgE) in addition to the two antibodies that are most predominant in circulating the blood, IgM and IgD.
  • Memory B cells that express the specific BCRs that were able to bind to the bacterial antigens.

Note:  Helper T cells are essential for the activation of B cells.  This becomes apparent in cases of human immunodeficiency virus (HIV), in that the HIV virus can destroy Helper T cells, leading to the inability of B cells to launch an effective humeral immunity.  Additionally, this lack of Helper T cells, leads to  diminished cytotoxic T cell mediated immune responses.  As such, individuals afflicted with HIV can become immunosuppressed and are vulnerable to both opportunistic infections and cancer.

Summary:

• CD4+ Helper T Cell Activation of Sensitized B Cells
  • Sensitized B Cells
    • B cells phagocytose pathogen, display bacterial peptides on MHC II
    • Sensitized B cells can be activated by Helper CD4+ T cells
  • Activation Process
    • Helper CD4+ T cells use TCR and CD4 co-receptors to bind peptide-MHC II on B cell
    • Release cytokines (e.g., interleukins) to activate B cells
    • Activated B cells proliferate into plasmablasts and memory B cells
  • Plasmablasts and Plasma Cells
    • Plasmablasts differentiate into plasma cells, produce antibodies
    • Plasma cells can produce ~100 million antibodies per hour
    • Cytokines help determine antibody types (IgG, IgA, IgE, IgM, IgD)
  • Memory B Cells
    • Express specific BCRs that bind infecting pathogen’s antigens, maintain memory pool
• Impact of HIV on Immune Response
  • HIV destroys Helper T cells, leading to impaired B cell activation and reduced CD8+ T cell activation
  • Results in diminished humoral immunity and cytotoxic T cell-mediated responses
  • Individuals with HIV are vulnerable to opportunistic infections and cancer